Dengue

engue is a mosquito-borne viral disease that can cause a severe flu-like fever. It is one of 17 diseases included in the World Health Organization (WHO) roadmap to overcome the global impact of neglected tropical diseases that can be effectively controlled.

Dengue thrives in poor urban areas in the tropics and subtropics. It is not restricted to those areas, however, as the vector mosquitoes are well adapted to the human environment and can occur in areas where there is better sanitation and quality of housing.

The incidence of dengue has increased 30-fold in the last 50 years, making it the most important mosquito-borne viral disease globally. More countries have reported their first outbreaks and the size of the outbreaks is causing severe economic disruption in many countries, according to WHO (Global strategy for dengue prevention and control 2012-2020).

Global burden of dengue

The number of reported cases has increased from around 1000 cases a year in the 1950s to over 3 million a year in 2015. Just nine countries reported dengue fever outbreaks before 1970 and it now occurs in at least 128 countries, putting 4 billion people at risk of the virus. This increase is partly attributed to the more recent requirement to report cases to WHO.

The reported cases, however, are generally considered to greatly underestimate the actual number of infections. This is due to under-reporting, misdiagnosis and patients not seeking treatment at a medical centre. Dengue symptoms are similar to many other viruses so there is thought to be a high number of cases of misdiagnosis.

WHO estimates 50-100 million cases of infection a year and 20,000 deaths, based on crude assumptions of risk. These are thought to be underestimates however due to lack of monitoring capability in many countries. A recent study estimated 300 million cases a year using a global model of dengue risk based on environmental and socioeconomic variables and known infection rates from published studies (Bhatt et al, 2013).

WHO plans to produce the first global dengue report at the end of 2017.

Occurrence of dengue globally using evidence-based consensus. (© Brady et al, 2012 Distributed under Creative Commons licence)

Dengue virus classification

The Dengue virus is a single strand RNA virus of the genus Flavivirus, family Flaviviridae. It is related to several other viruses transmitted by insects such as yellow fever, Zika, Japanese encephalitis and West Nile viruses.

There are four serotypes of the virus, called DEN-1, DEN-2, DEN-3 and DEN-4. Infection by one serotype gives lifelong immunity to that one, but only partial and temporary immunity to the others. After the temporary immunity has worn off, infection from these other serotypes can result in severe dengue infection.

Dengue transmission

Dengue is transmitted from human to human by mosquitoes, mainly in the genus Aedes. Ae aegypti and Ae. albopictus are the most prolific dengue vectors as they have adapted to urban environments around the world. They are especially suited to urban areas that lack reliable water supplies, and have poor waste management and sanitation.

Other species known to transmit the dengue virus include:

• Aedes polynesiensis in French Polynesia and the Cook Islands
• Aedes scutellaris in New Guinea
• Aedes hensilli in Micronesia
• Aedes furcifer and Aedes luteocephalus in western Africa.

Each species has its own characteristic behaviour and ecology. They can transmit multiple viruses including dengue, yellow fever, Chikungunya and other flaviviruses and also the human lymphatic filariasis parasite.

Aedes aegypti

Ae. aegypti originated in West Africa and is thought to have been carried around the world on sailing ships. It is now one of the most widespread mosquito species globally. It occurs in the tropics and subtropics, mainly between latitudes 35°N and 35°S below 1000m, but has been found up to 45°N in warmer months. The range approximately corresponds to a winter isotherm of 10°C.

It was established as far north as southern Europe from the late 18th to the mid-20th century before largely disappearing in the 1950s due to widespread use of organochlorine insecticides. There have only been sporadic records of occurrence since then in places such as Italy, Israel, Turkey, Netherlands and even southern England, mostly around ship ports. Recently it has established in Georgia and north-eastern Turkey, according to the European Centre for Disease Prevention and Control (ECDC).

The mosquito’s native habitat is tropical forests, near human habitation where it breeds in tree holes that contain water. This makes it suitably adaptable to the human environment where its main breeding grounds are man-made containers that can hold water — for example, pots, water tanks, toilet cisterns, cans, jars and tyres, whether around homes and businesses or as urban waste.

Ae. aegypti is rarely found more than 100m from human habitation and is thought to have a flight range of only 200m. It readily enters buildings to rest and feed so can get some protection from adverse weather when indoors. It is a daytime feeder, with peak feeding times early morning and evening. It can feed on multiple people during each breeding session and take multiple bites during feeding.

Aedes albopictus

Ae. albopictus, the Asian tiger mosquito, is native to tropical and subtropical areas of Southeast Asia. It has spread the dengue virus around the world to cooler climatic areas due to the ability of the eggs to withstand many months without water and the mosquito to tolerate freezing temperatures in microhabitats.

It has spread from Southeast Asia to other areas in Asia, Africa, the Americas and Europe on the back of international trade in goods that can carry water — such as used tyres carrying rainwater and decorative bamboo plants in pots. Antarctica is the only continent where it does not occur.

The water attracts the females to lay eggs on surfaces close to the water line in the country of origin. The durability of the eggs enables them to survive a long sea journey to the country of delivery, where they hatch out when stimulated by water entering their container.

Feeding

A female mosquito catches the virus by taking a blood meal from an infected human. The virus then has an incubation period in the mosquito, called the extrinsic incubation period (EIP). The virus first invades the cells lining the mosquito’s midgut and over 8 to 12 days spreads around its body. A study by the US CDC and Emory University found the incubation period in the mosquito ranged from 5 to 33 days at 25°C and 2 to 15 days at 30°C.

When the dengue virus reaches the mosquito’s salivary glands the mosquito becomes infectious. The female mosquito can then transmit the virus through further bites and remains infective for life.

Dengue symptoms and diagnosis

Dengue symptoms can be confused with other vector-borne viral and parasitic diseases, such as malaria, Chikungunya virus and Zika virus. Often a laboratory diagnosis is required to confirm a dengue infection, with different tests used at different stages of the disease.

Following the bite of an infected mosquito there is an incubation period in humans, called the intrinsic incubation period (IIP), before symptoms show. This lasts 4 to 10 days according to WHO and 3 to 14 days according to the CDC. Research by the CDC and Emory University found that 95% of IIPs are in the 3 to10 day range.

Symptoms last for 2 to 7 days and are classified into three phases: febrile, critical and recovery.

Febrile phase

In the febrile phase dengue can cause high fever (40°C/ 104°F) accompanied by symptoms such as severe headache, muscle and joint pain, nausea, vomiting, rash. The severity in individuals varies greatly, from asymptomatic all the way to life threatening. In some cases dengue fever then progresses into a critical phase when it appears if the fever is reducing, also called severe dengue or dengue haemorrhagic fever.

Recovery

A recovery phase can last a few days when fluid is reabsorbed into the bloodstream.

For more details on dengue disease see the WHO guidelines: Dengue. Guidelines for diagnosis, treatment, prevention and control.

Protection from dengue

Dengue vaccine

There is a vaccine available in some countries. The first vaccine was registered for use in Mexico, Brazil, Philippines and Thailand in 2015 and 2016. Dengvaxia (CYD-TDV), manufactured by Sanofi Pasteur, is recommended for use only in endemic areas with a high burden of disease and for people aged 9 to 45 years.

Dengue treatment

There is no specific treatment for dengue fever. Antiviral medicines that target RNA viruses are under development, but will take years to get to market.

Patients should drink plenty of fluids, rest and seek medical advice.

Health services can greatly reduce mortality rates by following WHO guidelines for clinical management:

• early clinical and laboratory diagnosis
• oral or intravenous rehydration during the plasma leakage phase
• staff training and
• hospital reorganization.

For further information refer to:

• WHO Guidelines for diagnosis, treatment, prevention and control
• WHO Dengue control
• Wikipedia: Dengue fever

Dengue vector control

Control of the vector mosquito populations requires not just the targeting of the Aedes mosquito breeding habitats and the adult stages, but also an integrated vector management approach that optimises the use of available resources and expertise.

Learn more about mosquito vector control.